Is hyping up medical research a crime? Why one CEO is under home arrest

CEO gets six months of home confinement over an allegedly misleading press release

Former InterMune CEO W. Scott Harkonen is spending six months in home confinement for overstating the benefits of a drug in a press release, and some worry that the case could be a sleeping threat to scientific free speech, David Brown writes in the Washington Post.

Fraud—despite no factual inaccuracies

In September 2009, Harkonen was found guilty of wire fraud for a press release in which he allegedly overstated the evidence supporting a drug manufactured by his company.

The press release at the center of the case described a clinical trial of interferon gamma-1b (sold as Actimmune) in 330 patients with idiopathic pulmonary fibrosis (IPF), a fatal lung condition diagnosed in about 50,000 Americans annually. The drug had FDA approval for use in two other rare inherited diseases and was prescribed off-label for IPF. InterMune was seeking agency approval for IPF, which Harkonen referred to as "a $2 billion market opportunity."

The study found that disease progression or death occurred in 46% of participants taking the drug and 52% of those on placebo—a statistically insignificant difference. However, when only patients with mild-to-moderate cases of the disease were considered, there was a more dramatic—and statistically significant—difference in survival: Just 5% of patients taking the drug died, compared with 16% of those taking a placebo.

The press release's two headlines emphasized the positive findings regarding the mild-to-moderate subgroup. Specifically, the headlines stated in bold-face letters: "InterMune Announces Phase III Data Demonstrating Survival Benefit of Actimmune in IPF." Following in italics, it stated: "Reduces Mortality by 70% in Patients with Mild to Moderate Disease."

The case has since wound its way through appeals and motions, with the 9th Circuit Court of Appeals eventually upholding his conviction. Last month, Harkonen's attorneys appealed the case to the Supreme Court.

If his appeals are unsuccessful, Harkonen will be barred from working as a pharmaceutical research and may not be able to work as a doctor, either.

Harkonen's crime: Data dredging

Harkonen's decision to focus on the subdivision of patients with mild-to-moderate disease is a controversial practice referred to as "data dredging," Brown explains. The term refers to the use of data mining to uncover relationships in data.

During the trial, government officials argued that if a trial misses all its "primary endpoints," then it is improper to draw conclusions about the drug's effect in subgroups identified after the trial was conducted. They also argued that Harkonen stood to benefit financially from placing a positive spin in the study. The press release stated that the study results would lead to peak sales of $400 to $500 million annually.

(Note: A later study focusing only on people with mild-to-moderated IPF failed to show improved survival rates in patients taking the drug. In fact, more participants taking the drug died than those taking placebos.)

Prosecution: Context matters

Both parties in the trial agreed that the press release was factually correct, but the prosecution argued that it lacked necessary context.

Harkonen's defense team pointed out that the press release acknowledged that the study's primary endpoints were not statistically significant. They argued that Harkonen was simply expressing an opinion on the usefulness of the company's drug that the government did not share.

"The fact that somebody else doesn't think the evidence is enough—does that foreclose you from holding a different view?" his attorney asked in an interview.

Stanford University'sSteven Goodman—who submitted a statement supporting Harkonen's recent appeal—notes that context includes what IPF patients are thinking. "Part of the issue goes to the level of proof a patient would need when facing a fatal disease with no treatment," he said, adding that lacking statistical significance "is far from proof that the treatment didn't work. And if I were a patient, I would want to know that."

A threat to scientific free speech?

The study has received little notice outside the world of pharmaceutical law, Brown writes. Still, some people view the case as a sleeping threat to free speech in science.

"If you applied this rule to scientists, a sizable proportion of them might be in jail today," Goodman told Brown. He added that the courts "don't quire realize the significance of what is in front of them or the furor that might erupt if this kooky precedent is allowed to stand" (Brown, Post, 9/23).